A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder

David Mischoulon, Catherine Best-Popescu, Michael Laposata, Wendelien Merens, Jessica L. Murakami, Shirley L. Wu, George I. Papakostas, Christina M. Dording, Shamsah B. Sonawalla, Andrew A. Nierenberg, Jonathan E. Alpert, Maurizio Fava

Research output: Contribution to journalArticle

70 Scopus citations


We examined the antidepressant efficacy and dose-response pattern of the n-3 docosahexaenoic acid (DHA). Thirty-five depressed adult outpatients (46% women; mean age 42 ± 14 years) with a 17-item Hamilton-Depression Scale (HAM-D-17) score of > /= 18 were randomized into one of three double-blind dosing arms for 12 weeks. Group A (n = 14): 1 g/day of oral DHA; Group B (n = 11): 2 g/day; and Group C (n = 10): 4 g/day. We measured HAM-D-17 scores, plasma DHA, eicosapentaenoic acid (EPA), and n-6/n-3 ratio. Completer response rates (> /= 50% decrease in HAM-D-17 score) were 83% for Group A, 40% for Group B, and 0% for Group C; Groups A and B had significant decreases in HAM-D-17 scores (p < 0.05). For completers and intent-to-treat subjects, plasma DHA increased significantly (p < 0.05), EPA had little change (p > 0.05), and n-6/n-3 decreased significantly (p < 0.05). DHA may be effective for depression at lower doses.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalEuropean Neuropsychopharmacology
Issue number9
StatePublished - Sep 2008
Externally publishedYes



  • Depression
  • DHA
  • Docosahexaenoic acid
  • Eicosapentaenoic acid
  • EPA
  • n-3
  • Omega-3

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)

Cite this

Mischoulon, D., Best-Popescu, C., Laposata, M., Merens, W., Murakami, J. L., Wu, S. L., Papakostas, G. I., Dording, C. M., Sonawalla, S. B., Nierenberg, A. A., Alpert, J. E., & Fava, M. (2008). A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. European Neuropsychopharmacology, 18(9), 639-645. https://doi.org/10.1016/j.euroneuro.2008.04.011